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Novel redox-sensing modules: accessory protein- and nucleic acid-mediated signaling.

ABSTRACT: SIGNIFICANCE: Organisms have evolved both enzymatic and nonenzymatic pathways to prevent oxidative damage to essential macromolecules, including proteins and nucleic acids. Pathways modulated by different protein-based sensory and regulatory modules ensure a rapid and appropriate response. RECENT ADVANCES: In contrast to classical two-component systems that possess internal sensory and regulatory modules, an accessory protein-dependent redox-signaling system has been recently characterized in bacteria. This system senses extracellular iron-mediated oxidative stress signals via an extracellularly located protein (HbpS). In vivo and in vitro studies allowed the elucidation of molecular mechanisms governing this system. Moreover, recent studies show that nucleic acids may also participate in redox-signaling during antioxidative stress response. CRITICAL ISSUES: Research for novel redox-signaling systems is often focused on known types of sensory and regulatory modules. It is also often considered that the oxidative attack of macromolecules, leading to modification and degradation processes, is the final step during oxidative stress. However, recent studies have demonstrated that oxidatively modified macromolecules can be intermediary states in the process of redox-signaling. FUTURE DIRECTIONS: Analyses of adjacent regions of genes encoding for known sensory and regulatory modules can identify potential accessory modules that may increase the complexity of sensing systems. Despite the fact that the involvement of DNA-mediated signaling in the modulation of one bacterial regulator protein has been analyzed in detail, further studies are necessary to identify additional regulators. Given the role of DNA in oxidative-stress response, it is tempting to hypothesize that RNA modules may also mediate redox-signaling.

SUBMITTER: Siedenburg G

PROVIDER: S-EPMC3277925 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Novel redox-sensing modules: accessory protein- and nucleic acid-mediated signaling.

Siedenburg Gabriele G Groves Matthew R MR Ortiz de Orué Lucana Darío D

Antioxidants & redox signaling 20120106 7

<h4>Significance</h4>Organisms have evolved both enzymatic and nonenzymatic pathways to prevent oxidative damage to essential macromolecules, including proteins and nucleic acids. Pathways modulated by different protein-based sensory and regulatory modules ensure a rapid and appropriate response.<h4>Recent advances</h4>In contrast to classical two-component systems that possess internal sensory and regulatory modules, an accessory protein-dependent redox-signaling system has been recently charac ...[more]

PMID: 22114914

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Project description:One challenge in studying chronic infectious and inflammatory disorders is understanding how host pattern recognition receptors (PRRs), specifically toll-like receptors (TLRs), sense and respond to pathogen- or damage-associated molecular patterns, their communication with each other and different components of the immune system, and their role in propagating inflammatory stages of disease. The discovery of innate immune activation through nucleic acid recognition by intracellular PRRs such as endosomal TLRs (TLR3, TLR7, TLR8, and TLR9) and cytoplasmic proteins (absent in melanoma 2 and DNA-dependent activator of interferon regulatory factor) opened a new paradigm: Nucleic acid sensing is now implicated in multiple immune and inflammatory conditions (e.g., atherosclerosis, cancer), viral (e.g., human papillomavirus, herpes virus) and bacterial (e.g., Helicobacter pylori, pneumonia) diseases, and autoimmune disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis). Clinical investigations reveal the overexpression of specific nucleic acid sensors in diseased tissues. In vivo animal models show enhanced disease progression associated with receptor activation. The involvement of nucleic acid sensors in various systemic conditions is further supported by studies reporting receptor knockout mice being either protected from or prone to disease. TLR9-mediated inflammation is also implicated in periodontal diseases. Considering that persistent inflammation in the oral cavity is associated with systemic diseases and that oral microbial DNA is isolated at distal sites, nucleic acid sensing may potentially be a link between oral and systemic diseases. In this review, we discuss recent advances in how intracellular PRRs respond to microbial nucleic acids and emerging views on the role of nucleic acid sensors in various systemic diseases. We also highlight new information on the role of intracellular PRRs in the pathogenesis of oral diseases including periodontitis and oral cavity cancer, which might offer future possibilities for disease prevention and therapy.

Dataset Information

Novel redox-sensing modules: accessory protein- and nucleic acid-mediated signaling.

Publications

Novel redox-sensing modules: accessory protein- and nucleic acid-mediated signaling.

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